Abnormal permeability of the blood-retinal barriers (BRB) and neovascularization are manifestations of blinding retinopathies in man such as diabetic retinopathy, retrolental fibroplasia, senile macular degeneration and sickle cell retinopathy. If successful preventative and therapeutic measures are to be developed, the mechanisms of abnormal permeability must be identified. Animal models provide the opportunity to clinically evaluate (as in man) the permeability of the BRB, and during any stage of the retinopathy to qualitatively and quantitatively delineate the morphologic characteristics associated with abnormal permeability. Vascular and neuroepithelial cell characteristics associated with BRB permeability include intercellular junctional complexes, cytoplasmic vesicles, and endothelial or neuroepithelial cell membrane surfaces. To explore pathways of abnormal BRB permeability, we propose to study clinically and morphologically 2 animal experimental retinopathies characterized by neovascularization and BRB abnormalities: phototoxic retinopathy in rats and retrolental fibroplasia in kittens. The qualitative presence of BRB abnormalities will be clinically ascertained during the time-course of the retinopathy by vitreous fluorophotometry and fundus fluorescein angiography using NaFl and FITC Dextrans of known molecular size. Fluorescent or electron dense permeability markers will be localized by fluorescence microscopy and electron microscopy. The latter technique will identify certain pathways whereby tracer has passed the BRB - e.g. gross widening or frank disruption of intercellular junctions, presence of endothelial cell fenestrations. The sensitive technique of electron microscopic stereology will quantitatively assess more subtle pathways such as cytoplasmic vesicular volume and surface area fenestrations and cell membrane infoldings. These studies will provide sensitive and quantitative correlation of abnormalities of permeability pathways in the BRB from the clinical to the ultrastructural level.